The release of 15-hydroxyeicosatetraenoic acid by human placental trophoblast is increased in preeclampsia.
OBJECTIVE
We tested the hypothesis that trophoblast produces 15-hydroxyeicosatetraenoic acid, and its level is elevated in trophoblast from preeclamptic women compared with normal. We also used selective enzymatic inhibitors to determine the relative contributions of 15-lipoxygenase and the two isozymes of prostaglandin H synthase to 15-hydroxyeicosatetraenoic acid levels.


METHODS
Cytotrophoblasts isolated from placentas of normal or preeclamptic women were cultured in the presence or absence of enzyme inhibitors. Media levels of 15-hydroxyeicosatetraenoic acid were measured by radioimmunoassay.


RESULTS
When compared with normal pregnancies, cytotrophoblasts from preeclamptic pregnancies released up to fivefold higher levels of 15-hydroxyeicosatetraenoic acid. Aspirin, an inhibitor of both the prostaglandin H synthase-1 and prostaglandin H synthase-2 isozymes, and nordihydroguaiaretic acid, a selective inhibitor of lipoxygenases, both significantly inhibited 15-hydroxyeicosatetraenoic acid production. In contrast, the selective prostaglandin H synthase-2 inhibitor NS-398 had no effect on 15-hydroxyeicosatetraenoic acid release in the absence of aspirin, but NS-398 reduced 15-hydroxyeicosatetraenoic acid levels in normal trophoblast pretreated with aspirin.


CONCLUSIONS
The data indicate that 15-hydroxyeicosatetraenoic acid is produced in trophoblasts and its release by cytotrophoblasts is higher in preeclamptic pregnancies compared with normal controls. Both lipoxygenase and prostaglandin H synthase contribute to 15-hydroxyeicosatetraenoic acid production, and aspirin reduces 15-hydroxyeicosatetraenoic acid secretion. We suggest 15-hydroxyeicosatetraenoic acid plays a role in the oxidation of lipoproteins and the endothelial damage characteristic of preeclampsia.
Johnson
R D
RD
Department of Obstetrics and Gynecology, St. Louis, MO 63110-1094, USA.
Polakoski
K L
KL
Huang
X
X
Sadovsky
Y
Y
Nelson
D M
DM
D001241:Aspirin / Q000494:pharmacology; D002478:Cells, Cultured; D016861:Cyclooxygenase Inhibitors / Q000494:pharmacology; D005260:Female; D006801:Humans; D006893:Hydroxyeicosatetraenoic Acids / Q000378:metabolism*; D007527:Isoenzymes / Q000037:antagonists & inhibitors / Q000502:physiology; D008084:Lipoxygenase / Q000502:physiology; D016859:Lipoxygenase Inhibitors / Q000494:pharmacology; D009637:Masoprocol / Q000494:pharmacology; D011225:Pre-Eclampsia / Q000378:metabolism* / Q000473:pathology; D011247:Pregnancy; D011451:Prostaglandin-Endoperoxide Synthases / Q000502:physiology; D011863:Radioimmunoassay; D013997:Time Factors; D014327:Trophoblasts / Q000166:cytology / Q000378:metabolism* / Q000473:pathology
D016861:Cyclooxygenase Inhibitors; D006893:Hydroxyeicosatetraenoic Acids; D007527:Isoenzymes; D016859:Lipoxygenase Inhibitors; C025984:15-hydroxy-5,8,11,13-eicosatetraenoic acid; D009637:Masoprocol; D008084:Lipoxygenase; D011451:Prostaglandin-Endoperoxide Synthases; D001241:Aspirin